Agonist and antagonist activity of en-clomiphene upon oestrogen-mediated events in the uterus, pituitary gland and brain of the rat.
The oestrogen agonist and antagonist activity of a single dose of en-clomiphene (0.5--50 mg/kg) was studied in peripheral and brain tissue in the 3 week ovariectomized rat. 17 beta-Oestradiol benzoate (100 microgram/kg) or vehicle was injected 24 h after en-clomiphene administration and data collected at 72 h. En-clomiphene produced a dose-related (agonist) fall in body weight and food intake. Agonist action was not observed upon sexual receptivity and prolactin secretion; oestrogen antagonism of these parameters was only seen at the higher doses. The effects of en-clomiphene upon serum LH and FSH were complex, both agonist and antagonist activity being demonstrated in the absence and presence of oestrogen. En-clomiphene was uterotrophic at all doses tested; however, oestrogen antagonism was only seen at the higher doses. Inhibition of the accumulation of uterine luminal fluid at the higher doses of en-clomiphene was a sensitive index of oestrogen antagonism. The results are discussed in relation to previous studies of the effects of en-clomiphene on oestrogen receptors. With the exception of the antagonism of oestrogen-induced sexual receptivity no correlation could be made between biological activity and the status of oestrogen receptors in tissue.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002369:Castration; D002996:Clomiphene / Q000494:pharmacology*; D064695:Enclomiphene; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D012726:Sexual Behavior, Animal / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D004965:Estrogen Antagonists; D006065:Gonadotropins, Pituitary; D002996:Clomiphene; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D064695:Enclomiphene